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Chomentowski 2011 J Clin Endocrinol Metab

From Bioblast
Publications in the MiPMap
Chomentowski P, Coen PM, Radiková Z, Goodpaster BH, Toledo FG (2011) Skeletal muscle mitochondria in insulin resistance: Differences in intermyofibrillar versus subsarcolemmal subpopulations and relationship to metabolic flexibility. J Clin Endocrinol Metab 96: 494-503.

» PMID: 21106709 Open Access

Chomentowski P, Coen PM, Radiková Z, Goodpaster BH, Toledo FG (2011) J Clin Endocrinol Metab

Abstract: CONTEXT: Insulin resistance is accompanied by lower lipid oxidation during fasting and metabolic inflexibility. Whether these abnormalities correlate with mitochondrial content in skeletal muscle is unknown.

OBJECTIVE: The objective of the study was to investigate whether decreased fasting lipid oxidation, metabolic inflexibility, and impaired glucose disposal correlate with reduced mitochondrial content in intermyofibrillar vs. subsarcolemmal (SS) subpopulations.

DESIGN: Forty sedentary adults with a wide spectrum of insulin sensitivity were studied: insulin-sensitive lean subjects, insulin-resistant nondiabetic subjects, and subjects with type 2 diabetes mellitus. Glucose disposal was measured by euglycemic clamp and [6,6-D(2)]-glucose methodology. Fuel oxidation and metabolic flexibility (during clamps) were assessed by indirect calorimetry. Maximum aerobic capacity was assessed by treadmill testing. Intermyofibrillar and SS mitochondrial content were measured by quantitative electron microscopy of muscle biopsy samples.

RESULTS: Intermyofibrillar mitochondrial content was lower in the insulin-resistant nondiabetic subjects and type 2 diabetes mellitus groups, significantly correlating with glucose disposal in both men (R = 0.72, P < 0.01) and women (R = 0.53, P < 0.01). In contrast, SS mitochondrial content was similar among groups. Lower intermyofibrillar mitochondrial content was not explained by mitochondrial size, altered fiber-type distribution, or differences in maximum aerobic capacity. Intermyofibrillar mitochondrial content was significantly correlated with fasting respiratory quotient (R = -0.46, P = 0.003) and metabolic flexibility (R = 0.38, P = 0.02).

CONCLUSIONS: In obese-insulin-resistant subjects with or without diabetes, intermyofibrillar mitochondrial content is decreased. This is not entirely explained by fitness status or fiber-type composition. SS mitochondrial content is unaffected, suggesting independent mitochondrial pool regulation. Lower mitochondrial content correlates with lower fasting lipid oxidation and metabolic inflexibility, suggesting it may be intrinsically linked to abnormal fuel utilization patterns of obesity-associated insulin resistance. Keywords: BMI, mitochondrial density

O2k-Network Lab: US FL Orlando Goodpaster BH

Labels: MiParea: mt-Biogenesis;mt-density, mt-Medicine  Pathology: Diabetes, Obesity 

Organism: Human  Tissue;cell: Skeletal muscle 

BMI, VO2max 

Lower mitochondrial content correlated with BMI.